Studies of the host response in man to infection with Plasmodium falciparum.
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Biomedical subjects
Publications and source records attributed to R Clancy.
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We describe the clinical syndrome, medical management, etiology, and neurologic outcome of stroke diagnosed by computed tomographic scan in 11 full-term neonates encountered during a two-year period. Neonatal stroke is relatively common and may appear in the setting of diverse cerebrovascular disorders such as hypoxic-ischemic encephalopathy, polycythemia, acute severe hypertension, and embolization. Repetitive, persistently unifocal motor seizures heralded localized cerebral injuries in eight infants. The majority of patients did not display any other lateralized clinical neurologic signs. An electroencephalogram revealed a focal or lateralized functional central nervous system abnormality in ten cases. All of the initial computed tomographic scans were focally abnormal. However, cranial ultrasound examinations were insensitive to stroke in nine patients. Medical management included careful cardiorespiratory support, correction of coexisting metabolic or system abnormalities, and aggressive administration of anticonvulsants to promptly eliminate seizures. Limited follow-up suggests that many affected infants may enjoy favorable outcomes.
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Culture adapted isolates of P. falciparum had different growth patterns (P less than 0.01) when cultured in the presence of sera obtained from 31 healthy Papua New Guinea residents. Both enhancement and suppression of growth was observed. Less variation was observed using an indirect immunofluorescent antibody method directed against schizont antigens, and no correlation between the two assays was found. This bioassay is assessed as a basis for serotyping P. falciparum strains.
The aims of this study were first, to assess whether or not immunoglobulin secretion from human gut mucosal B lymphocytes can be modified by T lymphocytes, and second whether human gut mucosal T lymphocytes are capable of regulating mucosal B lymphocyte function. T and B lymphocyte enriched cell populations were isolated from gut mucosa and co-cultured in varying proportions. Addition of T lymphocytes to B enriched mucosal cell populations (ratio B:T = 2:1) showed that mucosal B lymphocytes were responsive to T cell 'help'. Addition of more T cells (ratio B:T = 2:10) suppressed immunoglobulin synthesis.
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A micro semiautomative assay of merozoite inhibition antibody has been developed, based on incorporation of radiolabeled isoleucine into parasite protein. The assay has been validated using 44 sera from healthy blood donors in Madang. Inhibition of uptake of label occurred in 43.2% of tests, while an enhancement of uptake was demonstrated in 4.7%. This assay has 'potential' for both seroepidemiological studies, and for providing a mechanism of biotyping wild isolates.
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Cells were isolated from human bronchus mucosa, and characterized according to a surface marker for sheep erythrocytes (T cells), to the presence of membrane associated immunoglobulin (B cells), and to the capacity to phagocytose latex particles (macrophages). The T lymphocytes were further characterized according to their capacity to bind to the Fc fragment of IgG, IgM, and IgA (T gamma, T mu, and T alpha cells, respectively). Less t alpha cells were found in acutely inflamed mucosa than in mucosa obtained from patients with chronic inflammatory, or neoplastic disease (p = less than 0.001).
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Immune complexes were detected in the sera of ten of 22 patients with acute pancreatitis using a Clq deviation assay. Five of these were positive using a second technique. There was no correlation between immune complexes and clinical or aetiological features of the pancreatitis. Two patients with immune complexes developed a benign and transient pancreatic polyarthritis. Immune complexes may provide one common path in the sequence of pathogenic events that lead to pancreatitis.
A 32-year-old woman presented with a five-year history of primary infertility. In addition to anovulation associated with hyperprolactinaemia, she was found to have high titres of anti-sperm antibodies of agllutinating and immobilizing types. These were present in both serum and cervical mucus. After the regular use of condoms for nine months, all antibody titres fell dramatically and immobilizing antibodies became undetectable. Successful pregnancy quickly ensued. This report documents in thorough detail for the first time the sequential antibody changes associated with successful occlusion therapy.
Current clinical interest in circulating immune complexes defines a need to develop immune complex assays suitable for use in routine clinical immunology laboratories. We describe one such assay based on the principle of immune complexes binding to radiolabelled C1q, using commercially available IgG-coated latex particles for competitive binding. The assay is simple, rapid, cheap, reproducible and sensitive (5 micrograms/ml). Specificity for both antibody and antigen was demonstrated and clinical value was proven with defined clinical groups.
The role played by dietary chemical factors in the pathogenesis of chronic idiopathic urticaria (CIU) was assessed in seventy-six patients by challenge Stable remission was first established by using an empirically established 'exclusion diet'. A diet modified to exclude those chemicals giving a positive response to challlenge was demonstrated to be of therapeutic value for time periods of up to 18 months. Re-testing twelve patients at 12 months indicated that most patients positive to salicylate or benzoate challenge retained this pattern of reactivity.
This overview of the current state of knowledge of the immune system as it is relevant to the oral cavity in health and disease, is presented to illustrate the significance of immunology to the practice of dentistry. Thus immunological mechanisms contribute in a major way to the pathogenesis of the two most common dental disorders and it may be that the ultimate control of dental caries may be through manipulation of the mucosal immune apparatus. Future advances require a clearer and more quantitative analysis of oral mucosal immunity in relation to health and disease.
Argument exists as to whether platelet damage in chronic idiopathic thrombocytopenic purpura (ITP) is mediated by an autoimmune response to platelet antigen or by immune complexes. We have studied thirty-nine patients with ITP for evidence of (i) sensitization to platelet antigen, using a macrophage migration inhibition factor (MIF) assay, (ii) circulating immune complexes, using a Clq deviation technique, and (iii) serum-induced platelet 'immunoinjury', using a 3H-serotonin release assay. Eighty-one per cent of the patient group had a migration index of less than 0.8 (normal range 0.8-1.3), while 91% of those tested had a serum factor (presumably immune complexes) which bound to labelled Clq. The serotonin release assay was abnormal in 32% of twenty-two patients, and the results of this test bore no clear relationship to either those of the Clq deviation test or the MIF results. We conclude that most patients with ITP are sensitized to platelet-associated antigen, and have circulating immune complexes. The contribution of these factors to platelet destruction and the nature of the antigen in the complexes remain to be demonstrated. The serotonin release assay is less sensitive, non-specific, and has limited value in the diagnosis of ITP.
The presence and significance of locally produced antisperm antibody in 20 well-documented infertile patients has been investigated. Sera and vaginal washings both from patients and from fertile controls were examined for antisperm antibody by means of four methods. Antisperm antibody was detected in 25% of the washings taken from infertile patients, but in none of those from fertile women. Detection of antibody by the microimmobilization technique discriminated best between infertile and fertile women both in serum (P=0.0166) and in washings (P=0.0166). The results of this study support the concept that locally produced antisperm antibody contributes to conception failure in a subgroup of infertile women, and that the routine study both of sera and of vaginal washings of infertile patients has practical value.